Early life exposure to clinical dose penicillin induces long-term changes in gut microbiota, brain neurochemistry and behavior

Antibiotics (AB) are the most frequently dispensed drugs in pediatric patients and there is currently increasing concern that AB exposure early in life may have long-term consequences for health. Epidemiological studies revealed that early life AB exposure increases the risk of developing allergies, inflammatory bowel diseases and obesity. The effects of AB on brain and behavior have been previously demonstrated in germ-free rodents or by administering very high doses of a cocktail of antibiotics to adults or adolescents. In this study, we investigated the long-term effects of a clinically relevant dose of penicillin administered early in life on the microbiome, gut, brain and behavior, in both male and female Balb/c mice. We found that AB had lasting significant effects on gut microbiota composition, modified the tight junctions of blood-brain barrier, induced inflammation in the frontal cortex and was associated with changes in brain neurochemistry (Crhr2, Bdnf, Avpr1b). Finally, AB-treated mice exhibited decreased anxiety-like behavior, reduced social behavior and preference for social novelty as well as an unexpected aggressive behavior. Supplementation with Lactobacillus rhamnosus JB-1TM during AB treatment restored certain biological and behavioral parameters. This study raises concerns that even clinically relevant doses of AB given in early life may have long-term effects on behavior, possibly through effects on the gut microbial ecosystem.